HGNC Approved Gene Symbol: MOG
Cytogenetic location: 6p22.1 Genomic coordinates (GRCh38): 6:29,657,092-29,672,365 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 6p22.1 | ?Narcolepsy 7 | 614250 | Autosomal dominant | 3 |
Myelin-oligodendrocyte glycoprotein (MOG), which is found on the surface of myelinating oligodendrocytes and external lamellae of myelin sheaths in the central nervous system, is a member of the immunoglobulin superfamily (Pham-Dinh et al., 1993).
Pham-Dinh et al. (1993) isolated bovine, mouse, and rat MOG cDNAs. The predicted sequences of the mature MOG proteins are highly conserved. All contain 2 transmembrane segments and have an N-terminal, extracellular region with characteristics of an immunoglobulin variable domain. The N terminus shows strong homology with the N terminus of butyrophilin (601610), a protein expressed in the lactating mammary gland.
Hilton et al. (1995) cloned a human MOG cDNA encoding a predicted polypeptide containing a signal peptide of 29 amino acids followed by 218 amino acids of mature protein. Like its bovine and murine counterparts, it contains an Ig-like domain and 2 putative transmembrane domains. It has a potential N-linked glycosylation site at asn31.
Despite the similar names, oligodendrocyte-myelin glycoprotein (OMG; 164345) is a separate protein encoded within a large intron of the NF1 gene (613113). The 2 glycoproteins are associated specifically with oligodendrocytes and myelin, but have quite different roles in myelinogenesis and are structurally unrelated (Pham-Dinh, 1994). MOG is an intrinsic membrane molecule with 2 transmembrane domains, whereas OMG is anchored in the outer leaflet of the plasma membrane through a glycophospholipid tail. OMG belongs to the family of proteins with a series of tandem leucine-rich repeats, while MOG is a member of the Ig superfamily.
By in situ hybridization, Pham-Dinh et al. (1993) localized the MOG gene to chromosome 6p22-p21.3 and the homologous mouse gene to band C of chromosome 17, within the M region of the mouse MHC. Mog was the first non-class I gene to be assigned to that region.
Pham-Dinh et al. (1995) refined the position of MOG by selecting YACs containing the gene. Physical mapping of the human MOG and the mouse Mog genes by characterization of these YAC clones indicated that the gene is located at the distal end of the MHC class Ib region in both species. The human MOG gene lies 60 kb telomeric to HLA-F in a head-to-head orientation; the mouse Mog gene lies 25 kb telomeric to H2-M5 in a tail-to-head orientation.
Roth et al. (1995) found that the primary nuclear transcript of the human MOG gene, extending from the putative start of transcription to the site of poly(A) addition, is 15,561 nucleotides long. The gene contains 8 exons (later shown to be 9 exons by Pham-Dinh et al., 1995); canonical intron/exon boundary sites are found at each junction. The introns vary in size from 242 to 6,484 bp and contain numerous repetitive DNA elements, including 14 Alu sequences within 3 introns. Another Alu element is located in the 3-prime untranslated region of the gene. The 5-prime-flanking region contains several consensus sequences possibly relevant to the transcription of the MOG gene, in particular, binding sites in common with other myelin gene promoters. Polymorphic intragenic dinucleotide (CA)n and tetranucleotide (TAAA)n repeats were identified and may prove useful for association and linkage studies.
Pham-Dinh et al. (1995) showed that the MOG gene spans about 17 kb and undergoes alternative splicing to produce 6 different transcripts, 1 of which involves a theretofore unknown exon.
Pham-Dinh et al. (1993) noted that MOG is a target antigen in experimental autoimmune encephalomyelitis and multiple sclerosis.
Pham-Dinh et al. (1993) demonstrated that the developmental pattern of MOG expression in the rat central nervous system coincides with the late stages of myelination.
Using genomewide linkage analysis followed by exome sequencing in affected members of a large Spanish family with narcolepsy and cataplexy (NRCLP7; 614250), Hor et al. (2011) identified a heterozygous mutation in the MOG gene (S133C; 159465.0001) that segregated with the disorder in the family. The findings suggested a role for myelin and oligodendrocytes in disease susceptibility to this neurobehavioral disorder.
In affected members of a large Spanish family with narcolepsy and cataplexy (NRCLP7; 614250), Hor et al. (2011) identified a heterozygous 398C-G transversion in the MOG gene, resulting in a ser133-to-cys (S133C) substitution at the tip of the solvent-exposed loop in the extracellular Ig-like domain. The mutation was predicted to cause abnormal protein folding and a nonfunctional protein. In vitro expression studies in murine oligodendroglial precursor cells demonstrated that the mutant protein was ectopically expressed in the cytoplasm, although membrane localization did not appear to be affected. Twelve family members had narcolepsy and cataplexy, 7 of whom were obese and 4 of whom had type 2 diabetes. All 11 affected members studied and 1 who did not completely fulfill the diagnostic criteria for narcolepsy carried the mutation, whereas all 14 unaffected family members studied did not have the mutation. Based on these findings, the authors suggested a major role for myelin and oligodendrocytes in narcolepsy.
Hilton, A. A., Slavin, A. J., Hilton, D. J., Bernard, C. C. A. Characterization of cDNA and genomic clones encoding human myelin oligodendrocyte glycoprotein. J. Neurochem. 65: 309-318, 1995. [PubMed: 7790876] [Full Text: https://doi.org/10.1046/j.1471-4159.1995.65010309.x]
Hor, H., Bartesaghi, L., Kutalik, Z., Vicario, J. L., de Andres, C., Pfister, C., Lammers, G. J., Guex, N., Chrast, R., Tafti, M., Peraita-Adrados, R. A missense mutation in myelin oligodendrocyte glycoprotein as a cause of familial narcolepsy with cataplexy. Am. J. Hum. Genet. 89: 474-479, 2011. Note: Erratum: Am. J. Hum. Genet. 91: 396 only, 2012. [PubMed: 21907016] [Full Text: https://doi.org/10.1016/j.ajhg.2011.08.007]
Pham-Dinh, D. Personal Communication. Paris, France 3/15/1994.
Pham-Dinh, D., Gaspera, B. D., De Rosbo, N. K., Dautigny, A. Structure of the human myelin/oligodendrocyte glycoprotein gene and multiple alternative spliced isoforms. Genomics 29: 345-352, 1995. [PubMed: 8666381] [Full Text: https://doi.org/10.1006/geno.1995.9995]
Pham-Dinh, D., Jones, E. P, Pitiot, G., Della Gaspera, B., Daubas, P., Mallet, J., Le Paslier, D., Lindahl, C. F., Dautigny, A. Physical mapping of the human and mouse MOG gene at the distal end of the MHC class Ib region. Immunogenetics 42: 386-391, 1995. [PubMed: 7590972] [Full Text: https://doi.org/10.1007/BF00179400]
Pham-Dinh, D., Mattei, M. G., Nussbaum, J. L., Roussel, G., Pontarotti, P., Roeckel, N., Mather, I. H., Artzt, K., Lindahl, K. F., Dautigny, A. Myelin/oligodendrocyte glycoprotein is a member of a subset of the immunoglobulin superfamily encoded within the major histocompatibility complex. Proc. Nat. Acad. Sci. 90: 7990-7994, 1993. [PubMed: 8367453] [Full Text: https://doi.org/10.1073/pnas.90.17.7990]
Roth, M.-P., Malfroy, L., Offer, C., Sevin, J., Enault, G., Borot, N., Pontarotti, P., Coppin, H. The human myelin oligodendrocyte glycoprotein (MOG) gene: complete nucleotide sequence and structural characterization. Genomics 28: 241-250, 1995. [PubMed: 8530032] [Full Text: https://doi.org/10.1006/geno.1995.1137]